Alzheimer's disease (AD) is the most widespread type of dementia in elderly population of the world. It is also among the most serious health problems in the industrialized nations including United States. This neurodegenerative disease is progressive, incurable and lethal. More than 5.1 million Americans suffer from AD and 100 million people worldwide, and this number is expected to increase dramatically by the year of 2050 (Brookmeyer et al., Alzheimer's & dementia: the Journal of the Alzheimer's Assoc. 7:61-73 (2011); Sperling et al., Alzheimer's and Dementia 7:280-292 (2011)).
AD is characterized by a broad number of clinical manifestations, such as a gradual loss of short-term memory, language problems, progressive difficulty performing familiar tasks, disorientation to time and place, impairments in abstract thinking, disturbances in behavior and personality, sleep disturbances, depression, anxiety, psychosis and dementia (Farlow, American Journal of Health-System Pharmacy:AJHP:Official Journal of the American Society of Health-System Pharmacists 55(Suppl 2):S5-10 (1998); Monien et al., Expert Review of Neurotherapeutics 6:1293-1306 (2006)). These symptoms result from significant morphological alterations of the brain tissue caused by processes related to formation of Amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs).
The destructive pathophysiological process is thought to last many years with nearly no specific symptoms before the clinical diagnosis of AD can be made. Since the deferential diagnosis for dementias heavily relies on clinical criteria it is often a complex and difficult process. Slow initiation of AD during the “preclinical” phase could provide a critical opportunity for therapeutic intervention. The treatment at the early stages of disease progression would be the most effective allowing interference with the pathological process before irreversible damage occurs and keeping patients in an independent functional state for as long as possible. Therefore, early diagnosis of AD in patients at risk is of great importance.
Intensive investigation by many research teams has been made to identify blood based biomarkers that can be used for clinical laboratory tests, including metabolomics and proteomic analyses (Banks et al., The Lancet 356:1749-1756 (2000); Sudworth et al., European Conference on Biomedical Optics (2005); Burns et al., J. Alzheimers Dis. 17:391-397 (2009); Zellner et al., Acta Neuropathol. 118:181-195 (2009); Blennow et al., Nature Reviews Neurology, 6:131-144 (2010)). Although applied methods are expensive with regard to time, labor and financial resources and thus difficult to translate into the clinical laboratory, the results of this study showed that such biomarkers exist and provided very promising opportunities in the field of AD diagnosis. Several chemical analytes showed the potential to be AD biomarkers, including oxidative stress biomarkers, metabolite profile and protein-expression profile (Burns et al., J. Alzheimers Dis. 17:391-397 (2009); Teunissen et al., Neurobiol. Aging 24:893-902 (2003); Irizarry, NeuroRx: The Journal of the American Society for Experimental NeuroTherapeutics 1:226-234 (2004); Britschgi et al., Arch. Neurol. 66:161-165 (2009); Kork et al., Current Alzheimer Research 6:519-524 (2009)). However, none of them was accepted as a specific diagnostic biomarker applicable for a routine diagnostic test of AD when evaluated separately.
The development of a universal test to detect the presence of an AD biomarker signature in blood would have tremendous utility. With respect to the complexity of pathophysiological processes during AD progression, the diagnostic strategy can benefit greatly from simultaneous detection of various serum or plasma biomarkers.
Recently, Raman spectroscopy has been proved to be very suitable to study biochemical signatures of a number of diseases. It has been applied to diagnose different types of cancer, diabetes, atherosclerosis, and Parkinson's disease (Koo et al., Diabetes Technol. Ther. 1:153-157 (1999); Pichardo-Molina et al., Lasers Med. Sci. 22:229-236 (2007); Schipper et al., Biomark. Med. 2:229-238 (2008)). Raman spectroscopy provides specific information on structure, conformation and composition of macromolecules such as nucleic acids, proteins and lipids. This information is unique for each molecule. Therefore, Raman spectroscopy can provide fingerprinting type of information for the current biochemical state of blood. A diagnostic blood test can then be made based on a comparison of the obtained spectroscopic changes in blood of patient under evaluation with a developed library of Raman spectroscopic signatures for AD.
Raman spectroscopy provides unique information on the overall biochemical composition of a biological sample including the variations in the structure and conformation of contributing biomolecules. Raman scattering of human serum arise from various biomacromolecules, such as proteins, nucleic acids and lipids. Typically, the Raman signal is relatively weak. Colloidal silver nanoparticles as a SERS-active substrate are typically used to enhance the Raman scattering.
The present invention is intended to overcome these and other deficiencies in the art.